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Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis

The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt mye...

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Autores principales: Karner, Kristin, George, Tracy I., Patel, Jay L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Laboratory Medicine 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660325/
https://www.ncbi.nlm.nih.gov/pubmed/31240877
http://dx.doi.org/10.3343/alm.2019.39.6.509
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author Karner, Kristin
George, Tracy I.
Patel, Jay L.
author_facet Karner, Kristin
George, Tracy I.
Patel, Jay L.
author_sort Karner, Kristin
collection PubMed
description The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy.
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spelling pubmed-66603252019-11-01 Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis Karner, Kristin George, Tracy I. Patel, Jay L. Ann Lab Med Review Article The broad dissemination of next-generation sequencing capability has increased recognition of clonal hematopoiesis in various clinical settings. In hematologically normal individuals, somatic mutations may occur at an increasing frequency with age in genes that are also commonly mutated in overt myeloid malignancies such as AML and MDS (e.g., DNMT3A, TET2, and ASXL1). This is referred to as clonal hematopoiesis of indeterminate potential (CHIP) and is a benign state; however, it carries a risk of progression to hematologic malignancy as well as mortality primarily because of increased cardiovascular events. In clinical settings, clonal hematopoiesis may be observed in cytopenic patients who do not otherwise meet the criteria for hematologic malignancy, a condition referred to as clonal cytopenias of undetermined significance (CCUS). Distinguishing CCUS from overt MDS or other myeloid neoplasms can be challenging because of the overlapping mutational landscape observed in these conditions. Genetic features that could be diagnostically helpful in making this distinction include the number and biological function of mutated genes as well as the observed variant allele frequency. A working knowledge of clonal hematopoiesis is essential for the diagnosis and clinical management of patients with hematologic conditions. This review describes the key characteristics of clonal hematopoiesis with particular focus on implications for differential diagnosis in patients with CHIP, idiopathic cytopenia, CCUS, and myeloid malignancy. The Korean Society for Laboratory Medicine 2019-11 2019-06-25 /pmc/articles/PMC6660325/ /pubmed/31240877 http://dx.doi.org/10.3343/alm.2019.39.6.509 Text en © The Korean Society for Laboratory Medicine http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Karner, Kristin
George, Tracy I.
Patel, Jay L.
Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis
title Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis
title_full Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis
title_fullStr Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis
title_full_unstemmed Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis
title_short Current Aspects of Clonal Hematopoiesis: Implications for Clinical Diagnosis
title_sort current aspects of clonal hematopoiesis: implications for clinical diagnosis
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660325/
https://www.ncbi.nlm.nih.gov/pubmed/31240877
http://dx.doi.org/10.3343/alm.2019.39.6.509
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